​Histone modification is an epigenetic mechanism that enables fine-tuning of gene expression by altering chromatin structure and the accessibility of DNA for transcription. Numerous chemical tools have been developed to study the function of histone modifying proteins and their roles in physiological and pathological states. Use this guide to learn about writers, erasers, and readers of two major forms of histone modification, methylation and acetylation, and determine the best chemical modulation strategy for your experiments.